Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle.

Grupp, I L; Im, Wook‐Bin; Lee, C O; Lee, S W; Pecker, Mark S.; Schwartz, Arnold

doi:10.1113/jphysiol.1985.sp015609

Cited by 86 publications

(38 citation statements)

References 32 publications

(55 reference statements)

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“…The steady state level of aNa in guinea-pig papillary muscle continuously stimulated at a frequency of 0.1 Hz was 7.8 + 2.0 mi. This value compares favorably with mean values reported for aNa: measurements of aNa include 5.7-8.5 mM in rabbit and guinea-pig ventricular muscles (LEE and FOZZARD, 1975;KLEBER, 1983;Grupp et al, 1985). In cardiac Purkinje fibers COHEN et al (1982) showed that aNa increased dependent on stimulation frequency and after cessation of stimulation the elevated aNa declined in an exponential manner.…”

Section: Discussionsupporting

confidence: 72%

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Changes in intra- and extracellular potassium and intracellular sodium activities induced by repetitive stimulation and their relation to membrane potential in guinea-pig papillary muscle.

et al. 1987

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We measured changes in membrane potential (MP), extra-and intracellular potassium and intracellular sodium ion activities (4, 4, and aNa) in papillary muscle of the guinea-pig heart induced by repetitive stimulation at various frequencies and periods in vitro, using doublebarrelled ion-selective microelectrodes. Stimulation (2-4 Hz) depolarized the cells, and termination of stimulation induced hyperpolarization. The a K and aNa (stimulated at 0.2 Hz) were 92.3 + 4.6 and 7.8 ± 2.0 mM (mean + S.D.), respectively. Prolongation of the stimulation period (0.5-2 min) increased aNa time-dependently, but there was no further increase by stimulation for longer than 3 min. The increase in aNa was dependent on stimulus frequency. After termination of the stimulation, aNa declined exponentially. a K slightly decreased by the stimulation (3-4 Hz). a K increased during the stimulation period, and decreased below the initial level after termination of the stimulation. Results suggest that in guineapig papillary muscle, the. contribution of an electrogenic component of Na-K pump to the hyperpolarization after stimulation would be small, since the hyperpolarization could be explained mostly by depletion of 4 induced by Na-K pump activity.

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Section: Discussionsupporting

confidence: 72%

“…), respectively. Both the values for aK and aNa were within the range reported for ventricular muscles using single-barrel ion-selective microelectrodes: for aK, 82.6-116 mM (LEE and FOZZARD, 1975;BROWNING and STRAUSS,1981;COHEN et al, 1982); and for aNa, 5.7-8.5 mM (LEE and FOZZARD, 1975;COHEN et al, 1982;KLEBER, 1983;GRUPP et al, 1985).…”

Section: Resultsmentioning

confidence: 56%

Changes in intra- and extracellular potassium and intracellular sodium activities induced by repetitive stimulation and their relation to membrane potential in guinea-pig papillary muscle.

et al. 1987

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“…Ouabain has been thought to increase the contraction through a Na+-Ca2+ exchange mechanism (Reuter & Seitz, 1968;Sheu & Fozzard, 1982;Wasserstrom et al, 1983;Eisner et al, 1984;Vassalle & Lee, 1984;Wier & Hess, 1984;Grupp et al, 1985). Ouabain inhibits Na'-K' ATPase and results in an accumulation of [NaJ]i.…”

Section: Discussionmentioning

confidence: 99%

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Kondo

Mizukami

Shibata

1990

British J Pharmacology

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The inhibitory effects of disopyramide on electromechanical responses were investigated in guinea‐pig papillary muscles driven by electrical stimuli. Disopyramide up to 10−5 m did not cause a negative inotropic effect, while the maximum upstroke velocity of the action potential (dV/dtmax) was significantly decreased. At higher concentrations, this drug dose‐dependently inhibited the contraction, and dV/dtmax was further decreased. This inhibition of contraction was accompanied by a depression of the slow action potential in partially depolarized preparations by increasing [K+]o (26 mm). In preparations pretreated with nifedipine (10−6 m) and ryanodine (10−6 m), the contraction was almost completely inhibited. In such preparations, ouabain (2 × 10−6 m) markedly increased the contraction, probably through the Na+‐Ca2+ exchange mechanism. This contraction was inhibited by disopyramide above 10−8 m, and an almost complete inhibition was caused at 3 × 10−5 m. A similar inhibitory effect was observed on the contraction increased by the lowering of [Na+]o (36 mm). These results suggest that disopyramide at high concentrations inhibits Ca influx through slow Ca2+ channels and at low concentrations, it reduces the contraction increased through the Na+‐Ca2+ exchange mechanism. Disopyramide had a greater effect on cardiac contractility mediated by the Na+‐Ca2+ exchange mechanism.

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“…Much of our present knowledge of cellular Na+ regulation has emerged from studies utilizing Na+-sensitive microelectrodes which allow intracellular Na+ activity (aNa) to be monitored continuously over time and sensitively enough to detect even small changes in ion activity. Na+-sensitive microelectrodes have proved to be a powerful tool in elucidating the mechanism of action of cardiac steroids (Lee, 1985) and particularly in resolving the controversial issue on the positive inotropic effect of low ouabain concentrations in rat heart (Grupp, Im, Lee, Lee, Pecker & Schwartz, 1985).…”

Section: Introductionmentioning

confidence: 99%

Intracellular sodium activity and its regulation in guinea‐pig atrial myocardium.

Wang

Schmied

Ebner

et al. 1993

The Journal of Physiology

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SUMMARY1. Intracellular Na' activity (aIa) and membrane resting potential were studied in quiescent guinea-pig atrial and papillary muscles by means of Na'-sensitive and conventional microelectrodes. The effects of the cardioactive steroid dihydroouabain (DH11) on aia, force of contraction and sarcolemmal Na', K+-ATPase activity were also investigated.2. In thirty atria and twenty-two papillary muscles, a'a amounted to 8-0 + 0 2 and 4 7 +0 3 mm, respectively (means±+S.E.M.). When both tissues were from the same animal, with the same ion-sensitive microelectrode mean a'a values of 79 + 02 and 541 + 0-5 mm (P < 0 0 1) were obtained from eight atrial and eight papillary muscles, respectively.3. Membrane resting potentials (Em) were significantly (P < 0-001) more negative in the papillary muscles (-83 5 + 0 7 mV; n = 8) than in the atrium (-7841 + 0 5 mV; n = 8). Deviation of Em from EK (determined by K+-sensitive microelectrodes) was 30 + ±0)2 mV in ventricular (P < 0 05) and 641 + 0 3 mV in atrial preparations (/' < 0 05).4. Inhibition of the Na+ pump by DHO increased aia of the atrium within 10 min by 06+01 (n = 7). 13+01 (n = 5) and 32+02 mm (n = 5) at 5,10 and 30jCtM, respectively. In the papillary muscle, 10 yUM DHO was without effect while a'a rose by 1-0+0-1 (n = 5) and 2-9+02 mm (n = 6) at 30 and 120 /aM DHO.5. Consistent with the a'a measurements, the potency of DHO to increase force of the isometric contraction was three times higher in atrium than in papillary muscle (stimulation frequency 0 2 Hz).6. Hydrolytic activity of sarcolemmal Na+,K+-ATPase isolated from atria amounted to only one third of that detected in ventricles (0-07 +001, n = 6, versus 0-2+0±-01 /mol phosphate released min-(g tissue)-', n = 5). The inhibitory potencies of DHO on sarcolemmal Na+,K+-ATPase preparations were found to be identical in the enzymes from either tissue.

show abstract

Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle.

Cited by 86 publications

References 32 publications

Changes in intra- and extracellular potassium and intracellular sodium activities induced by repetitive stimulation and their relation to membrane potential in guinea-pig papillary muscle.

Changes in intra- and extracellular potassium and intracellular sodium activities induced by repetitive stimulation and their relation to membrane potential in guinea-pig papillary muscle.

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Intracellular sodium activity and its regulation in guinea‐pig atrial myocardium.

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